Subclonal patterns in follow-up of acute myeloid leukemia combining whole exome sequencing and ultrasensitive IBSAFE digital droplet analysis

Research output: Contribution to journalArticle


We studied mutation kinetics in ten relapsing and four non-relapsing patients with acute myeloid leukemia by whole exome sequencing at diagnosis to identify leukemia-specific mutations and monitored selected mutations at multiple time-points using IBSAFE droplet digital PCR. Five to nine selected mutations could identify and track leukemic clones prior to clinical relapse in 10/10 patients at the time-points where measurable residual disease was negative by multicolor flow cytometry. In the non-relapsing patients, the load of mutations gradually declined in response to different therapeutic strategies. Three distinct patterns of relapse were observed: (1) one or more different clones with all monitored mutations reappearing at relapse; (2) one or more separate clones of which one prevailed at relapse; and (3) persistent clonal hematopoiesis with high variant allele frequency and most mutations present at relapse. These pilot results demonstrate that IBSAFE analyses detect leukemic clones missed by flow cytometry with possible clinical implications.Highlights The IBSAFE ddPCR MRD method seems applicable on virtually all newly diagnosed AML patients and was more sensitive than flow cytometry. Monitoring a few mutations captured the kinetics of the evolving recurrent leukemia. NPM1-mutation alone may not be a reliable MRD-marker.


External organisations
  • Halmstad County Hospital
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
  • Medical Genetics


  • AML, clonal patterns, ddPCR, genetic evolution, MRD, subclones
Original languageEnglish
JournalLeukemia and Lymphoma
Publication statusE-pub ahead of print - 2020 May 19
Publication categoryResearch

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